American football head impacts tied to increased brain damage and cognitive decline

Research suggests that reduced brain clearance, indicated by increased perivascular space volume, may be the missing link between repetitive head impacts and cognitive decline in former American football players.

Study: Repetitive head impacts and perivascular space volume in former American Football players. Image credits: Gorodenkoff / Shutterstock.com

From a recent study published in JAMA network openedResearchers are investigating how repetitive head impacts (RHI) alter perivascular space (PVS) volume, cognition, and associated neurodegeneration in former American football players.

RHI and the perivascular system

Exposure to RHI during contact sports increases the risk of developing dementia because tau protein builds up in the brain. Nevertheless, the specific pathophysiological pathways contributing to neurodegeneration remain unclear; therefore, further research is needed to elucidate how brain protein concentrations change after RHI.

RHI-induced PVS changes may contribute to neurodegenerative processes and future cognitive loss in affected individuals. Previous studies report that changes in PVS may increase the risk of cognitive decline and dementia.

Furthermore, perivascular transport supports the elimination of harmful proteins from the brain in Alzheimer’s disease (AD) and after severe traumatic brain injury (TBI). However, there remains a lack of research on whether exposure to RHI alters the perivascular transport or architecture of this system.

About the study

The current cross-sectional study was a subset of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation (DIAGNOSE) of Chronic Traumatic Encephalopathy (CTE) study, which was conducted over seven years at four sites in the United States . This study included former professional and collegiate football players, while age-matched men without exposure to RHI served as a control group.

Male subjects between the ages of 45 and 74, who weighed 400 pounds or less and were fluent in English were invited to participate in the study. None of the study participants had contraindications to positron emission tomography (PET), magnetic resonance imaging (MRI), or lumbar puncture.

Professional athletes played football for twelve or more years, with at least three seasons at the college level and four seasons in the National Football League. Collegiate athletes had similar guidelines, requiring six or more years of organized football play.

Exclusion criteria included neurological disorders, hearing or vision disorders, comorbidities such as endocrine, metabolic or infectious diseases, liver, kidney or lung disorders, and cancer.

Data was obtained between September 2016 and February 2020 and analyzed from May 2021 to October 2023. The study exposure consisted of repeated head impacts while playing American football. RHI exposure was determined using indices of cumulative head impact count (CHII), rotational acceleration (CHII-R), and linear acceleration (CHII-G).

Primary outcome measures included PVS volume in the white matter of the brain, based on structural MRI findings. Cognitive performance assessments include the Montreal Cognitive Assessment (MoCA), Neuropsychological Assessment Battery (NAB) List Learning Test, Trail Making Tests, and the Stroop Color and Word Test. MoCA assessed general cognitive function, while NAB assessed episodic memory and the remaining two tests measured executive function.

Linear regression analysis measured associations between PVS volume and neuropsychological assessments in previous American football players. Study covariates included age, education, body mass index (BMI), blood pressure, diabetes, hypercholesterolemia, antihypertensive and antidiabetic agents, blood-brain barrier (BBB) ​​permeable β-blockers, imaging site, and apolipoprotein ε4 (APOE ε4) status .

Findings of the study

The study cohort consisted of 224 individuals with an average age of 57 years, of whom 170 were former football players and 54 controls, respectively. Of the former football players, 114 were professional players and 56 were university level players.

Former football players had higher PVS volume than controls, with a mean difference of 0.3. Increased CHII-G and CHII-R levels were associated with increased PVS volume in former football players. During an American football career an increase of 440,000 g in CHII-G or 35 million radians/s² in CHII-R resulted in a one standard deviation increase in PVS volume.

The researchers observed a relationship between PVS volume and cumulative head impact force, while no relationship was observed with head impact frequency. Thus, the number of head blows may have less influence on PVS volume than the total force of all head blows.

PVS volume was higher among older football players prescribed antihypertensive medications. In comparison, the use of β-blockers was significantly related to reduced PVS volume, indicating a potential protective effect of this class of drugs.

Older age, positive APOE ε4 carriage, and higher BMI significantly influenced the relationship between CHII-R and PVS. Similarly, age and positive APOE ε4 carriage significantly influenced the relationship between CHII-G and PVS.

Previous American football players with higher PVS volume performed worse cognitively on the MoCA and Trail Making tests. Overall, the study results indicate that higher PVS volume was associated with inferior general cognitive and executive skills.

Conclusions

Previous American football players had higher RHI exposure and higher PVS volume than unexposed controls. Furthermore, RHI exposure positively correlated with PVS volume, which is associated with poorer overall cognitive and executive performance.

The present study suggests that increased PVS may reflect reduced clearance of neurotoxic waste products, which may increase the risk of neurodegenerative processes. Interestingly, use of β-blockers was related to significantly smaller PVS; therefore, future studies could investigate the effects of beta-blockers on the treatment of RHI.